AU2008206406A1 - Antiviral nucleoside analogs - Google Patents
Antiviral nucleoside analogs Download PDFInfo
- Publication number
- AU2008206406A1 AU2008206406A1 AU2008206406A AU2008206406A AU2008206406A1 AU 2008206406 A1 AU2008206406 A1 AU 2008206406A1 AU 2008206406 A AU2008206406 A AU 2008206406A AU 2008206406 A AU2008206406 A AU 2008206406A AU 2008206406 A1 AU2008206406 A1 AU 2008206406A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- substituted
- compound
- aryl
- pct
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002777 nucleoside Substances 0.000 title claims description 14
- 150000003833 nucleoside derivatives Chemical class 0.000 title description 11
- 230000000840 anti-viral effect Effects 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 135
- -1 NH 2 Chemical group 0.000 claims description 126
- 125000003118 aryl group Chemical group 0.000 claims description 69
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 67
- 229940002612 prodrug Drugs 0.000 claims description 58
- 239000000651 prodrug Substances 0.000 claims description 58
- 125000001072 heteroaryl group Chemical group 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000003342 alkenyl group Chemical group 0.000 claims description 37
- 125000000304 alkynyl group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 125000003107 substituted aryl group Chemical group 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 30
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 30
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
- 229910003827 NRaRb Inorganic materials 0.000 claims description 25
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 208000036142 Viral infection Diseases 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 22
- 230000009385 viral infection Effects 0.000 claims description 22
- 241001465754 Metazoa Species 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 235000000346 sugar Nutrition 0.000 claims description 16
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 14
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 13
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 12
- 229960000329 ribavirin Drugs 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 229910052701 rubidium Inorganic materials 0.000 claims description 11
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 239000001226 triphosphate Substances 0.000 claims description 10
- 230000003612 virological effect Effects 0.000 claims description 10
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 9
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- OOUNPZOLTCEMSL-UHFFFAOYSA-N 2-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound CC1(O)C(O)COC1CO OOUNPZOLTCEMSL-UHFFFAOYSA-N 0.000 claims description 8
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 8
- 125000000539 amino acid group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims description 8
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 7
- 102000014150 Interferons Human genes 0.000 claims description 7
- 108010050904 Interferons Proteins 0.000 claims description 7
- 108020000999 Viral RNA Proteins 0.000 claims description 7
- 239000001177 diphosphate Substances 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 229910052702 rhenium Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 208000005176 Hepatitis C Diseases 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 239000003443 antiviral agent Substances 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- DLMDGLJCWXETIS-UHFFFAOYSA-N triazine-5-carboxylic acid Chemical compound OC(=O)C1=CN=NN=C1 DLMDGLJCWXETIS-UHFFFAOYSA-N 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 241000710886 West Nile virus Species 0.000 claims description 4
- 101150068479 chrb gene Proteins 0.000 claims description 4
- 208000002672 hepatitis B Diseases 0.000 claims description 4
- 229940079322 interferon Drugs 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
- 235000011178 triphosphate Nutrition 0.000 claims description 4
- LFRDGHVRPSURMV-YFKPBYRVSA-N (4s)-4,5-dihydroxypentanal Chemical compound OC[C@@H](O)CCC=O LFRDGHVRPSURMV-YFKPBYRVSA-N 0.000 claims description 3
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 3
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- 208000000474 Poliomyelitis Diseases 0.000 claims description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 3
- 241000700647 Variola virus Species 0.000 claims description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 3
- 230000000340 anti-metabolite Effects 0.000 claims description 3
- 229940100197 antimetabolite Drugs 0.000 claims description 3
- 239000002256 antimetabolite Substances 0.000 claims description 3
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 claims description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 229930014626 natural product Natural products 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003835 nucleoside group Chemical group 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 3
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 3
- KDKMTIRSYIHSTB-MROZADKFSA-N (2r,3r,4r)-2,3,4,5-tetrahydroxypentanethial Chemical group OC[C@@H](O)[C@@H](O)[C@@H](O)C=S KDKMTIRSYIHSTB-MROZADKFSA-N 0.000 claims description 2
- SQXRWAVEVYDDBF-LMVFSUKVSA-N (2r,3r,4r)-2-fluoro-3,4,5-trihydroxypentanethial Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](F)C=S SQXRWAVEVYDDBF-LMVFSUKVSA-N 0.000 claims description 2
- NJYXSKVOTDPOAT-WDCZJNDASA-N (2s,3r,4r)-2-fluoro-3,4,5-trihydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](F)C=O NJYXSKVOTDPOAT-WDCZJNDASA-N 0.000 claims description 2
- SQXRWAVEVYDDBF-WDCZJNDASA-N (2s,3r,4r)-2-fluoro-3,4,5-trihydroxypentanethial Chemical compound OC[C@@H](O)[C@@H](O)[C@H](F)C=S SQXRWAVEVYDDBF-WDCZJNDASA-N 0.000 claims description 2
- BKNVTPUCZNUJMP-WHFBIAKZSA-N (2s,4s)-2-fluoro-4,5-dihydroxypentanethial Chemical compound OC[C@@H](O)C[C@H](F)C=S BKNVTPUCZNUJMP-WHFBIAKZSA-N 0.000 claims description 2
- MJMJUKHABPJQGX-CRCLSJGQSA-N (3s,4r)-3-fluoro-4,5-dihydroxypentanal Chemical compound OC[C@@H](O)[C@@H](F)CC=O MJMJUKHABPJQGX-CRCLSJGQSA-N 0.000 claims description 2
- JBFNVLCLNHQXCH-CRCLSJGQSA-N (3s,4r)-3-fluoro-4,5-dihydroxypentanethial Chemical compound OC[C@@H](O)[C@@H](F)CC=S JBFNVLCLNHQXCH-CRCLSJGQSA-N 0.000 claims description 2
- XFBDCPQESJYXPC-YFKPBYRVSA-N (4s)-4,5-dihydroxypentanethial Chemical compound OC[C@@H](O)CCC=S XFBDCPQESJYXPC-YFKPBYRVSA-N 0.000 claims description 2
- LPXOUBDTZSHIOQ-UHFFFAOYSA-N 1,2,4-triazine-5-carbonitrile Chemical compound N#CC1=CN=NC=N1 LPXOUBDTZSHIOQ-UHFFFAOYSA-N 0.000 claims description 2
- AAYFBWZEIFWMPD-UHFFFAOYSA-N 2-(hydroxymethyl)-4-methyloxolane-3,4-diol Chemical compound CC1(O)COC(CO)C1O AAYFBWZEIFWMPD-UHFFFAOYSA-N 0.000 claims description 2
- UADBLZFWTJHOJC-UHFFFAOYSA-N 2-(hydroxymethyl)cyclopentan-1-ol Chemical group OCC1CCCC1O UADBLZFWTJHOJC-UHFFFAOYSA-N 0.000 claims description 2
- OIEIKVCEXBMETK-BYPYZUCNSA-N 2-[(1s)-1,2-dihydroxyethoxy]acetaldehyde Chemical compound OC[C@@H](O)OCC=O OIEIKVCEXBMETK-BYPYZUCNSA-N 0.000 claims description 2
- VQKBTEBRZHBIGE-BYPYZUCNSA-N 2-[(1s)-1,2-dihydroxyethyl]sulfanylacetaldehyde Chemical compound OC[C@@H](O)SCC=O VQKBTEBRZHBIGE-BYPYZUCNSA-N 0.000 claims description 2
- NGWKEVMCTIVMBA-UHFFFAOYSA-N 2-fluoro-4-(hydroxymethyl)pyrrolidin-3-ol Chemical compound OCC1CNC(F)C1O NGWKEVMCTIVMBA-UHFFFAOYSA-N 0.000 claims description 2
- DWROYQTVCUQGJR-UHFFFAOYSA-N 3-(hydroxymethyl)cyclopent-3-ene-1,2-diol Chemical group OCC1=CCC(O)C1O DWROYQTVCUQGJR-UHFFFAOYSA-N 0.000 claims description 2
- MZQHDBUGKAFSOC-UHFFFAOYSA-N 3-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound OCC1CCC(O)C1O MZQHDBUGKAFSOC-UHFFFAOYSA-N 0.000 claims description 2
- BORAVSBFYTYKOE-UHFFFAOYSA-N 4-(hydroxymethyl)cyclopenten-1-ol Chemical group OCC1CC=C(O)C1 BORAVSBFYTYKOE-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 241001115402 Ebolavirus Species 0.000 claims description 2
- 241001466953 Echovirus Species 0.000 claims description 2
- 241000709661 Enterovirus Species 0.000 claims description 2
- 229930010555 Inosine Natural products 0.000 claims description 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 2
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 claims description 2
- 108010078233 Thymalfasin Proteins 0.000 claims description 2
- 102400000800 Thymosin alpha-1 Human genes 0.000 claims description 2
- GAADRFVRUBFCML-UHFFFAOYSA-N [2-(hydroxymethyl)cyclobutyl]methanol Chemical compound OCC1CCC1CO GAADRFVRUBFCML-UHFFFAOYSA-N 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 230000001093 anti-cancer Effects 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- LMYOLOWXQDLHKQ-UHFFFAOYSA-N cyclopent-2-en-1-ylmethanol Chemical group OCC1CCC=C1 LMYOLOWXQDLHKQ-UHFFFAOYSA-N 0.000 claims description 2
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 claims description 2
- CCRXJMDIIXJVIC-CRCLSJGQSA-N diazonio-[(2s,3s)-1,2-dihydroxy-5-oxopentan-3-yl]azanide Chemical compound OC[C@@H](O)[C@H](CC=O)N=[N+]=[N-] CCRXJMDIIXJVIC-CRCLSJGQSA-N 0.000 claims description 2
- 229940125697 hormonal agent Drugs 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 229960003786 inosine Drugs 0.000 claims description 2
- 238000013160 medical therapy Methods 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 150000004712 monophosphates Chemical group 0.000 claims description 2
- GUFUWKKDHIABBW-UHFFFAOYSA-N pyrrolidin-1-ylmethanol Chemical compound OCN1CCCC1 GUFUWKKDHIABBW-UHFFFAOYSA-N 0.000 claims description 2
- QOTUIIJRVXKSJU-UHFFFAOYSA-N pyrrolidin-3-ylmethanol Chemical group OCC1CCNC1 QOTUIIJRVXKSJU-UHFFFAOYSA-N 0.000 claims description 2
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims description 2
- 229950006081 taribavirin Drugs 0.000 claims description 2
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims description 2
- 229960004231 thymalfasin Drugs 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 4
- 229940124683 HCV polymerase inhibitor Drugs 0.000 claims 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims 2
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- NJYXSKVOTDPOAT-LMVFSUKVSA-N (2r,3r,4r)-2-fluoro-3,4,5-trihydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](F)C=O NJYXSKVOTDPOAT-LMVFSUKVSA-N 0.000 claims 1
- PYMIDWYUQAHNQK-WHFBIAKZSA-N (2s,4s)-2-fluoro-4,5-dihydroxypentanal Chemical compound OC[C@@H](O)C[C@H](F)C=O PYMIDWYUQAHNQK-WHFBIAKZSA-N 0.000 claims 1
- IXDZFGATLNCIOI-NGJCXOISSA-N (3r,4r,5r)-3,4,5,6-tetrahydroxyhexan-2-one Chemical compound CC(=O)[C@H](O)[C@H](O)[C@H](O)CO IXDZFGATLNCIOI-NGJCXOISSA-N 0.000 claims 1
- IJIHMDVMMUTJEJ-UHFFFAOYSA-N 1,2,4-triazine-5-carboxamide Chemical compound NC(=O)C1=CN=NC=N1 IJIHMDVMMUTJEJ-UHFFFAOYSA-N 0.000 claims 1
- UMZKOJVNUVDHED-UHFFFAOYSA-N 1,2,4-triazine-5-carboximidamide Chemical compound NC(=N)C1=CN=NC=N1 UMZKOJVNUVDHED-UHFFFAOYSA-N 0.000 claims 1
- DITIGNGDSVRJFX-UHFFFAOYSA-N 3-(hydroxymethyl)-4-methylidenecyclopentane-1,2-diol Chemical compound OCC1C(O)C(O)CC1=C DITIGNGDSVRJFX-UHFFFAOYSA-N 0.000 claims 1
- ZBAXTIFHKIGLEJ-UHFFFAOYSA-N 3-(hydroxymethyl)cyclopentan-1-ol Chemical compound OCC1CCC(O)C1 ZBAXTIFHKIGLEJ-UHFFFAOYSA-N 0.000 claims 1
- UKDQIWLEEJYIDQ-UHFFFAOYSA-N 4-(hydroxymethyl)pyrrolidine-2,3-diol Chemical group OCC1CNC(O)C1O UKDQIWLEEJYIDQ-UHFFFAOYSA-N 0.000 claims 1
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims 1
- GJAYIOSSXMTWIH-BXXZVTAOSA-N N(=[N+]=[N-])C(=S)[C@H](O)[C@H](O)[C@H](O)CO Chemical compound N(=[N+]=[N-])C(=S)[C@H](O)[C@H](O)[C@H](O)CO GJAYIOSSXMTWIH-BXXZVTAOSA-N 0.000 claims 1
- AHYCTNVIMLVRSL-UHFFFAOYSA-N OCC1CC(O)N(F)C1 Chemical compound OCC1CC(O)N(F)C1 AHYCTNVIMLVRSL-UHFFFAOYSA-N 0.000 claims 1
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 claims 1
- 102000012479 Serine Proteases Human genes 0.000 claims 1
- 108010022999 Serine Proteases Proteins 0.000 claims 1
- 108010011222 cyclo(Arg-Pro) Proteins 0.000 claims 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 107
- 235000019439 ethyl acetate Nutrition 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
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- Public Health (AREA)
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- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| TW200942243A (en) | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
| US20090247750A1 (en) * | 2008-03-28 | 2009-10-01 | Biocryst Pharmaceuticals, Inc. | Process for preparing nucleoside analogs |
| HUE025528T2 (en) | 2008-04-23 | 2016-05-30 | Gilead Sciences Inc | 1'-substituted carba-nucleoside analogs for antiviral treatment |
| EP2313102A2 (en) | 2008-07-03 | 2011-04-27 | Biota Scientific Management | Bycyclic nucleosides and nucleotides as therapeutic agents |
| PE20161067A1 (es) | 2009-02-10 | 2016-10-23 | Gilead Sciences Inc | Analogos carba-nucleosidicos para tratamiento antiviral |
| ME01528B (me) | 2009-09-21 | 2014-04-20 | Gilead Sciences Inc | POSTUPCI l INTERMEDIJERI ZA PROIZVODNJU 1'-CIJANOKARBANUKLEOZIDIH ANALOGA |
| MX352646B (es) | 2009-09-21 | 2017-12-04 | Gilead Sciences Inc | Analogos de carba-nucleosidos sustituidos con 2'-fluoro para tratamiento antiviral. |
| US7973013B2 (en) | 2009-09-21 | 2011-07-05 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
| US8455451B2 (en) | 2009-09-21 | 2013-06-04 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
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| EA026523B1 (ru) | 2010-09-20 | 2017-04-28 | Джилид Сайэнс, Инк. | 2'-фторзамещенные карбануклеозидные аналоги для противовирусного лечения |
| CA2812962C (en) | 2010-09-22 | 2020-03-31 | Alios Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
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| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
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| EA038045B1 (ru) | 2015-02-20 | 2021-06-28 | Инсайт Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
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| MX2009007333A (es) | 2009-08-31 |
| HK1138286A1 (en) | 2010-08-20 |
| PT2114980E (pt) | 2012-09-25 |
| CY1113282T1 (el) | 2016-04-13 |
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| JP2010515760A (ja) | 2010-05-13 |
| CA2674589A1 (en) | 2008-07-24 |
| EP2535345A1 (en) | 2012-12-19 |
| IL199664A0 (en) | 2010-04-15 |
| US20100015094A1 (en) | 2010-01-21 |
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| US8440813B2 (en) | 2013-05-14 |
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| EP2114980A2 (en) | 2009-11-11 |
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| CN101611046A (zh) | 2009-12-23 |
| PL2114980T3 (pl) | 2012-11-30 |
| WO2008089105A3 (en) | 2008-09-12 |
| EP2114980B1 (en) | 2012-06-27 |
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